MicroRNA collected from the synovial fluid of patients with active Borrelia burgdorferi (Lyme) infections was indicative of acute inflammation related to the killing of bacteria by antibiotics.
However, microRNA collected in patients’ synovial fluid after treatment with antibiotics for B. burgdorferi where arthritis persists more closely resembles that seen in chronic inflammatory states and is characterized by synovial proliferation and a breakdown of the wound repair process.
The robust immune response that bodies produce when confronted by a bacterial infection are necessary defenses, but if they persist, they can also lead to tissue damage.
Joint pain or arthritis associated with B. burgdorferi (Lyme disease) infection most often resolves with antibiotic treatment. The pathogenic processes associated with antibiotic-refractory Lyme arthritis have not previously been described.
Robert Lochhead and colleagues in New England pointed out that microRNAs have a vital role in gene expression and “provide robustness” to gene regulation by inhibiting or facilitating transcription.
A previous study found that rheumatoid arthritis had the most robust enrichment of microRNA-target gene risk factor of any disease ever studied. This evidence points to a crucial role for microRNA defects in the pathogenesis of inflammatory disease.
The authors presented the results of their investigation into the differences between synovial microRNA expression in the joints of patients with active Lyme arthritis and with antibiotic-refractory Lyme arthritis in a recent Arthritis & Rheumatology article.
Ultimately, 32 patients who had Lyme arthritis and synovial fluid or synovial tissue available were included. Patients were divided into 3 groups; group 1 patients were referred prior to antibiotic therapy, group 2 consisted of patients whose arthritis persisted after antibiotic treatment, and group 3 was composed of patients who required synovectomies after 2 or 3 months of antibiotic therapy.
• In groups 1 and 2, synovial fluid levels of microRNA-146a, microRNA-155, microRNA-142, microRNA-17, and microRNA-20a correlated positively with longer arthritis duration after oral antibiotic treatment.
• There was a negative correlation between B. burgdorferi immune globulin G antibody titers and microRNA-155 (r=-0.490, P=0.04), microRNA-146a (r=-0.49, P=0.04), and microRNA-142 (r=-0.54, P=0.02).
The NIH; the Littauer Foundation; the Roland Foundation; the English, Bonter, Mitchell Foundation, and Massachusetts General Hospital supplied funding for this study.
Robert B. Lochhead, Klemen Strle, Nancy D. Kim, et al. “MicroRNA Expression Shows Inflammatory Dysregulation and Tumor-Like Proliferative Responses in Joints of Patients With Postinfectious Lyme Arthritis.” Arthritis Rheumatol. 2017;69:1100-1110. doi: 10.1002/art.40039.